Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 19, 2022
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Sinupol (Ota/Miyaoka), trans-α-Himachalene (Bach), Laurencenone C (List), Lamellodysidine A (Sugita), Kingianin A (Zhao/Chen/Lu), Sordaricin (Houk/Tang)

Sinupol (3), isolated from the soft coral Sinularia polydactyla, showed moderate inhibitory activity toward protein tyrosine phosphatase 1B. Koichiro Ota and Hiroaki Miyaoka of the Tokyo University of Pharmacy and Life Sciences used the Evans protocol to prepare 1, securing the absolute configuration of the final product, then cyclized 1 to 2 (Synlett 2020, 31, 1007, DOI: 10.1055/s-0037-1610757; Synthesis 2022, 54, 689, DOI: 10.1055/a-1643-5729).

Thorsten Bach of the Technical University of Munich showed that under irradiation, the cycloheptenone 4 was converted to its trans isomer, that readily underwent intermolecular Diels-Alder cycloaddition with the diene 5, leading to 6. The ketone 6 was carried on to trans-α-himachalene (7) (J. Org. Chem. 2022, 87, 4838. DOI: 10.1021/acs.joc.2c00186).

Benjamin List of the Max-Planck-Institut für Kohlenforschung devised a Binol-derived imidodiphosphorimidate catalyst that directed the absolute sense of the cycloaddition of the α-methylidene ketone 8 with isoprene 9, to give 10. The ketone 10 was carried on to laurencenone C (11) (J. Am. Chem. Soc. 2022, 144, 6703. DOI: 10.1021/jacs.2c01971).

Lamellodysidine A (14), isolated from the marine sponge Lamellodysidea herbacea collected in Indonesia, showed cytotoxic and antimicrobial activity. En route to 14, Kazuyuki Sugita of Hoshi University cyclized the triene 12 to the lactone 13 (Org. Lett. 2022, 24, 921. DOI: 10.1021/acs.orglett.1c04289).

Kingianin A (15), isolated from the bark of Endiandra kingiana Gamble, a tree collected in the rain forest of Pahang State in Malaysia, showed selective cytotoxicity toward certain lung cancer cell lines. Jinbo Zhao of the Changchun University of Technology and Qin Chen and Ping Lu of Fudan University devised an oxazaborolidinium catalyst that mediated the absolute sense of the addition of the cyclobutenone 12 to butadiene 13, leading to the ester 14 and thus to 15 (Synthesis 2022, 54, 1977. DOI: 10.1055/s-0041-1737339).

The biosynthesis of sordaricin (17), the precursor to the antifungal sordarin, had long been known to proceed via cyclization of the triene 16. K. N. Houk and Yi Tang of UCLA have now identified the "Diels-Alderase" enzyme that mediates the cycloaddition, allowing the efficient production of 17 in cell culture (Nature Commun. 2022, 13, 2568. DOI: 10.1038/s41467-022-30288-6).

D. F. Taber, Org. Chem. Highlights 2022, December 19.